2-79086471-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006507.4(REG1B):​c.217G>T​(p.Val73Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

REG1B
NM_006507.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.400
Variant links:
Genes affected
REG1B (HGNC:9952): (regenerating family member 1 beta) This gene is a type I subclass member of the Reg gene family. The Reg gene family is a multigene family grouped into four subclasses, types I, II, III and IV based on the primary structures of the encoded proteins. This gene encodes a protein secreted by the exocrine pancreas that is highly similar to the REG1A protein. The related REG1A protein is associated with islet cell regeneration and diabetogenesis, and may be involved in pancreatic lithogenesis. Reg family members REG1A, REGL, PAP and this gene are tandemly clustered on chromosome 2p12 and may have arisen from the same ancestral gene by gene duplication. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2785778).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
REG1BNM_006507.4 linkuse as main transcriptc.217G>T p.Val73Leu missense_variant 4/6 ENST00000305089.8 NP_006498.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
REG1BENST00000305089.8 linkuse as main transcriptc.217G>T p.Val73Leu missense_variant 4/61 NM_006507.4 ENSP00000303206 P1
REG1BENST00000476554.1 linkuse as main transcriptn.629G>T non_coding_transcript_exon_variant 3/31
REG1BENST00000479258.5 linkuse as main transcriptn.324G>T non_coding_transcript_exon_variant 4/41
REG1BENST00000454188.5 linkuse as main transcriptc.70G>T p.Val24Leu missense_variant 2/43 ENSP00000387410

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461696
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727152
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152246
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 26, 2021The c.217G>T (p.V73L) alteration is located in exon 4 (coding exon 3) of the REG1B gene. This alteration results from a G to T substitution at nucleotide position 217, causing the valine (V) at amino acid position 73 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.61
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.16
.;T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.78
T;T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.28
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.7
.;M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-2.4
N;N
REVEL
Benign
0.089
Sift
Benign
0.076
T;D
Sift4G
Uncertain
0.055
T;T
Polyphen
0.72
.;P
Vest4
0.29
MutPred
0.78
.;Gain of sheet (P = 0.1539);
MVP
0.12
MPC
0.012
ClinPred
0.39
T
GERP RS
2.6
Varity_R
0.19
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs546205053; hg19: chr2-79313597; COSMIC: COSV59307698; COSMIC: COSV59307698; API